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The physical chemistry of corticosteroid-cyclodextrin complexes: The Host-guest Chemistry of Corticosteroid and Cyclodextrin Systems Elucidated with NMR and Applied to Novel Surface-decorated Surface Enhanced Raman Spectroscopic Probes

Eteer, Shahrazad A.
Publication Date
End of Embargo
Supervisor
Scowen, Ian J.
Munshi, Tasnim
Telford, Richard
Keywords
Corticosteroids, HFA, Complexation, Cyclodextrins, Inhalation, pMDI, NMR, SERS, Nanoparticles
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Creative Commons License
The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
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Accepted for publication
Institution
University of Bradford
Department
Faculty of Life Sciences
Awarded
2018
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Abstract
Inhaled corticosteroids (ICS) are used to address inflammatory illnesses including asthma and COPD, with delivery commonly achieved using pressurised metered dose inhalers (pMDI). Hydrofluoroalkanes (HFAs) have been introduced as an alternative propellant to chlorofluorocarbons (CFCs) to reduce their environmental impact. However, the thermodynamic properties of HFAs are poorly understood and are different to those of CFCs. It is essential, therefore, to characterise the drugs and excipients used in HFA inhalers in order to obtain a comprehensive understanding of the device performance and the therapeutic efficacy. This work has developed different analytical methods to study the complexation between ICS and CD which are added to enhance the solubility of inhaled drugs in pMDI propellant systems providing rational control of suspension vs. solution formulations and hence their dose uniformity and stability. The Nuclear Magnetic Resonance (NMR) method developed has shown weaker complexation between budesonide and the derivatised CDs DIMEB and TRIMEB in organic solvents compared to D2O with the strength of the complex formed being ranked as D2O > MeOD > CDCl3 > CD3CN. The derivatisation of the CD also shows a marked difference in complexation with budesonide with the strength of the association being ranked as DIMEB > βCD > TRIMEB. Studies of various ICS compounds with TRIMEB in the fluorinated propellant HPFP showed the association to be greatest in budesonide, followed by beclomethasone dipropionate, momestasone furoate and fluticasone propionate. Surface-enhanced Raman scattering (SERS) has been used for the detection of corticosteroids in water using thiol functionalised βCD as a complementary study to NMR. This has been utilised to evaluate the host-guest complexes formed and provides further insight into the complexation of the compounds by their inclusion into the CD cavity. The structural data obtained using the NMR and SERS approaches developed have provided a fundamental insight into the physical chemistry of these interactions at a molecular level.
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http://hdl.handle.net/10454/17379
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Type
Thesis
Qualification name
PhD
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